The long term goals for this work is to determine whether our gene delivery vector technologies are efficient and safe for creating large transgenic animals, specifically chickens, pigs, and goats. This project is the next step in testing these new gene delivery vectors on their way for use in human gene therapy. However, success in the large animals in this project would yield immediate opportunities in the therapeutic protein production, agriculture improvement, and disease model creation markets. The Stealth Gene and Targeted Gene Delivery (TGD) vector technologies enable high efficiency gene delivery into whole, adult animals. Both integrate the delivered DNA directly into the genome with Stealth Gene being random and TGD being targeted via homologous recombination. The integration frequency is 5 to 10-fold higher using Stealth Gene over TGD. However, for human gene therapy applications the lower efficiency may be outweighed by the better safety profile associated with targeted, homologous gene delivery. Both of these vectors show extraordinary results in small animals such as mice and rats. Based on these observations, this project is to test whether these gene delivery vectors will work in large animals that have huge commercial value and is the next step for human clinical applications. Specifically, we will examine the vector's ability to deliver an exogenous gene into the epidermis, reproductive tissues, and milk producing tissues. The integration frequency of the marker gene and its expression will be examined. The results of these experiments will be assessed using standard techniques at the molecular and cellular levels. These results will be the basis for deciding whether this technology shows promise to expand testing in large animals and eventually begin testing in people. [unreadable] [unreadable]